The effect of artificial gravity on plasma and tissue lipids in rats: The Cosmos 936 experiment

Plasma and tissue lipids in male SPF Wistar rats flown for 18.5 days aboard the Cosmos 936 biosatellite were analyzed. One group of rats was subjected to artificial gravity by use of a centrifuge during the flight. An experiment simulating known space flight factors other than weightlessness was done on Earth. An increase of total cholesterol in plasma, of nonesterified fatty acids in plasma and brown adipose tissue, of triacylglycerols in plasma, liver, thymus and bone marrow was noted several hours after biosatellite landing. Smaller changes were observed in the terrestrial control experiment. With the exception of triacylglycerol accumulation in bone marrow, these increases disappeared 25 days after biosatellite landing. Exposing the rats aboard the biosatellite to artificial gravity was beneficial in the sense that such exposure inhibited the phospholipid and triacylglycerol increase in plasma and inhibited the increase of triacylglycerol in liver and especially in bone marrow.     

Space flight experiment on Chinese silkworm on board the Russian 10th Biosatellite.

Space flight experiments on Chinese silkworm (Bombyx mori L.) were conducted on board the Russian 10th Biosatellite for 12 days. The samples included silkworm eggs, larvae, cocoons, pupae and moths. The processes of spinning, cocooning, mating, oviposition, larval hatching, pupation and moth emergence all completed well in space. The following effects of space flight on silkworm development were observed: The times of hatching and oviposition in the flight group were 2 to 3 days earlier than in the control group; the hatching rate of diapause eggs during space flight seemed higher than that of the control group; the life span of 2 of the 7 varieties flown was shortened; genetical variations appeared in 3 varieties. The results showed that the embryonic stage was probably the period most sensitive to the space flight environment.     

Urodelean amphibians in studies on microgravity: effects upon organ and tissue regeneration.

Results obtained from nine experiments performed onboard Russian biosatellites have shown that microgravity promotes tissue regeneration in the newt, Pleurodeles waltl. The effect has been reproduced in all flights and on a clinostat as well for eye tissues (lens and retina), limbs and tail. The effect was demonstrated in 1.5- to 2-fold increase in cell proliferation in the early stages of regeneration in space flight. Animals "flown" intact and operated after flight regenerated faster than control ones and showed long-lasting micro-"g" effect. The most recent experiment flew aboard the Bion-11 biosatellite. This test was performed for study on microgravity effect on neural retina regeneration after optic nerve lesioning in the newt. Obtained results confirmed our previous information about intensification of regenerative processes in detached neural retina in urodela exposed to simulated weightlessness (Grigoryan et al., 1998). In particular, we found the increase and activation of cell populations participating in neural retina restoration and maintenance of retinal structure. Our findings suggest that promoting effect of microgravity upon regeneration could be influenced by several factors, largely influenced by a response of the whole organism to changed gravity vector. We hypothesized the synthesis of the specific range of stress proteins induced by micro-"g" and their regulative role in cell proliferation. Such a hypothesis for the existence of "altered gravity stress proteins" is discussed.     

Blood and clonogenic hemopoietic cells of newts after the space flight.

Ribbed newts were used for studying the effect of space flight on board of the biosatellite (Cosmos-2229) on blood and clonogenic hemopoietic cells. In blood of newts of the flight group, the relative proportion of neutrophils increased, whereas that of lymphocytes and eosinophils decreased. Space flight did not result in loss of the ability of newt blood cells to incorporate H3-thymidine. Analysis of clonogenic hemopoietic cells was performed using the method of hemopoietic colony formation on cellulose acetate membranes implanted into the peritoneal cavity of irradiated newts. To analyze reconstitution of hemopoiesis after irradiation donor hemopoietic cells from flight or control newts were transplanted into irradiated newts whose hemopoietic organs were investigated. The newt can be considered an adequate model for studying hemopoiesis under the conditions of the space flight.     

Studies toward birth and early mammalian development in space.

Sustaining life beyond Earth on either space stations or other planets will require a clear understanding of how the space environment affects key phases of mammalian reproduction and development. Pregnancy, parturition (birth) and the early development of offspring are complex processes essential for successful reproduction and the proliferation of mammalian species. While no mammal has yet undergone birth within the space environment, studies spanning the gravity continuum from 0- to 2-g are revealing startling insights into how reproduction and development may proceed under gravitational conditions deviating from those typically experienced on Earth. In this report, I review studies of pregnant Norway rats and their offspring flown in microgravity onboard the NASA Space Shuttle throughout the period corresponding to mid- to late gestation, and analogous studies of pregnant rats exposed to hypergravity (hg) onboard the NASA Ames Research Center 24-ft centrifuge. Studies of postnatal rats flown in space or exposed to centrifugation are reviewed. Although many important questions remain unanswered, the available data suggest that numerous aspects of pregnancy, birth and early mammalian development can proceed under altered gravity conditions.     

Controllable passive detectors for study of the radiation environment in space and the atmosphere

We propose to study the radiation environment on board different flight vehicles: cosmos-type satellites, orbital stations, Space Shuttles and civil (sonic and supersonic) aircraft. These investigations will be carried out with single type of passive detector, namely, nuclear photoemulsions (NPE) with adjustable threshold of particle detection within broad range of linear energy transfer (LET) that is done by means of the technique of selective development of NPE exposed in space.

These investigations will allow one to determine:

• integral spectra of LET of charged particles of cosmic ray (CR) over a wide range from 2.0 to 5×10⁴ MeV/cm in biological tissue;

• differential energy spectra of fast neutrons (1–20 MeV);

• estimation of absorbed and equivalent doses from charged and neutral component CR;

• charge and energy spectra of low energy nuclei (E≤100 MeV) with Z≥2 having in view the extreme hazard radiation to biological objects and microelectronic schemes taken on board inside and outside of these different flight vehicles with exposures from several days to several months.

The investigation of radiation environment on board the airplanes depending on the flight parameters will be conducted using emulsions of different sensitivity without any controlling of threshold sensitivity (Akopova et al., 1996). The proposed detector can be used in the joint experiments on the new International Cosmic Station “Alpha”.     

Radiation measurements on the flight of IML-2.

The second flight of the International Microgravity Laboratory (IML-2) on Space Shuttle flight STS-65 provided a unique opportunity for the intercomparison of a wide variety of radiation measurement techniques. Although this was not a coordinated or planned campaign, by sheer chance, a number of space radiation experiments from several countries were flown on this mission. There were active radiation measuring instruments from Japan and US, and passive detectors from US, Russia, Japan, and Germany. These detectors were distributed throughout the Space Shuttle volume: payload bay, middeck, flight deck, and Spacelab. STS-65 was launched on July 8, 1994, in a 28.45 degrees x 306 km orbit for a duration of 14 d 17 hr and 55 min. The crew doses varied from 0.935 mGy to 1.235 mGy. A factor of two variation was observed between various passive detectors mounted inside the habitable Shuttle volume. There is reasonable agreement between the galactic cosmic ray dose, dose equivalent and LET spectra measured by the tissue equivalent proportional counter flown in the payload bay with model calculations. There are significant differences in the measurements of LET spectra measured by different groups. The neutron spectrum in the 1-20 MeV region was measured. Using fluence-dose conversion factors, the neutron dose and dose equivalent rates were 11 +/- 2.7 microGy/day and 95 +/- 23.5 microSv/day respectively. The average east-west asymmetry of trapped proton (>3OMeV) and (>60 MeV) dose rate was 3.3 and 1.9 respectively.     

Review of primary spaceflight-induced and secondary reloading-induced changes in slow antigravity muscles of rats.

We have examined the light and electron microscopic properties of hindlimb muscles of rats flown in space for 1-2 weeks on Cosmos biosatellite flights 1887 and 2044 and Space Shuttle missions Spacelab-3, Spacelab Life Sciences-1 and Spacelab Life Sciences-2. Tissues were obtained both inflight and postflight permitting definition of primary microgravity-induced changes and secondary reentry and gravity reloading-induced alterations. Spaceflight causes atrophy and expression of fast fiber characteristics in slow antigravity muscles. The stresses of reentry and reloading reveal that atrophic muscles show increased susceptibility to interstitial edema and ischemic-anoxic necrosis as well as muscle fiber tearing with disruption of contractile proteins. These results demonstrate that the effects of spaceflight on skeletal muscle are multifaceted, and major changes occur both inflight and following return to Earth's gravity.     

Accommodations for earth-viewing payloads on the international space station

The design of the International Space Station (ISS) includes payload locations that are external to the pressurized environment. These external or attached payload accommodation locations will allow direct access to the space environment at the ISS orbit and direct viewing of the earth and space. NASA sponsored payloads will have access to several different types of standard external locations; the S3 Truss Sites, the Columbus External Payload Facility (EPF), and the Japanese Experiment Module Exposed Facility (JEM-EF). As the ISS Program develops, it may also be possible to locate external payloads at the P3 Truss Sites or at non-standard locations similar to the handrail-attached payloads that were flown during the MIR Program. Earth-viewing payloads may also be located within the pressurized volume of the US Lab in the Window Observational Research Facility (WORF). Payload accommodations at each of the locations will be described, as well as transport to and retrieval from the site.     

Changes in the numbers of osteoclasts in newts under conditions of microgravity.

Intensity of osteoclastic resorption and calcium content were investigated in intact limb bones of the newts flown on board of a biosatellite Cosmos-2229 after amputation of their forelimbs and tail. Using X-ray microanalysis it was shown an increase in calcium content in the bones on 20th day after operation. Histological study revealed an activation of osteoclastic resorption on endosteal surface of long bones. The newts exposed after surgery on a biosatellite had the same level of bone mineralisation as operated ground control ones, but the increase in number of polynuclear osteoclasts was lower.     

Effects of exercise equipment on the microgravity environment.

Numerous types of exercise equipment have flown on manned space flights to evaluate and maintain crew members' physical condition while on orbit. Vibrations associated with the use of some exercise equipment cause concern among microgravity scientists who are usually looking for a quiescent environment in which to run their experiments. We discuss the impact of aerobic (bicycle ergometer, treadmill) and non-aerobic (resistance devices) exercise on the microgravity environment of the Space Shuttle Orbiters and the Mir Space Station. In general, characteristic vibration disturbances due to ergometer exercise show the pedalling frequency at 2.5 to 3 Hz and the crew members' body rocking side-to-side at about half the pedalling frequency. For treadmill exercise, the footfall frequency on the treadmill platform can be clearly seen in the 1 to 2 Hz range, along with upper harmonics. The use of resistance exercise devices does not typically cause vibrations. Several vibration isolation systems used on the Orbiters and planned for the International Space Station are introduced. Finally, the responses of specific experiments to exercise vibrations are outlined.     

Microgravity effects on Drosophila melanogaster development and aging: comparative analysis of the results of the Fly experiment in the Biokosmos 9 biosatellite flight.

The results are presented of the exposure of Drosophila melanogaster to microgravity conditions during a 15-day biosatellite flight, Biokosmos 9, in a joint ESA-URSS project. The experimental containers were loaded before launch with a set of Drosophila melanogaster Oregon R larvae so that imagoes were due to emerge half-way through the flight. A large number of normally developed larvae were recovered from the space-flown containers. These larvae were able to develop into normal adults confirming earlier results that Drosophila melanogaster of a wild-type constitution can develop normally in the absence of gravity. However, microgravity exposure clearly enhances the number of growing embryos laid by the flies and possibly slows down the developmental pace of the microgravity-exposed animals. Due to some problems in the experimental set-up, this slowing down needs to be verified in future experiments. No live adult that had been exposed to microgravity was recovered from the experiment, so that no life span studies could be carried out, but adult males emerged from the recovered embyros showed a slight shortening in life span and a lower performance in other experimental tests of aging. This agrees with the results of previous experiments performed by our groups.     

Commercial involvement in the development of space-based plant growing technology.

Considerable technological progress has been made in the development of controlled environment facilities for plant growth. Although not all of the technology used for terrestrial facilities is applicable to space-based plant growth facilities, the information resident in the commercial organizations that market these facilities can provide a significant resource for the development of the plant growing component of a CELSS. In 1985, NASA initiated an effort termed the Centers for the Commercial Development of Space (CCDS). This program endeavors to develop cooperative research and technology development programs with industrial companies that capitalize on the strengths of industry-university working relationships. One of the these CCDSs, the Wisconsin Center for Space Automation and Robotics (WCSAR), deals with developing automated plant growth facilities for space, in cooperation with several industrial partners. Concepts have been developed with industrial partners for the irradiation, water and nutrient delivery, nutrient composition control and automation and robotics subsystems of plant growing units. Space flight experiments are planned for validation of the concepts in a space environment.     

Structural and functional organisation of regenerated plant protoplasts exposed to microgravity on Biokosmos 9.

Preparatory experiments for the IML-1 mission using plant protoplasts, were flown on a 14-day flight on Biokosmos 9 in September 1989. Thirty-six hours before launch of the biosatellite, protoplasts were isolated from hypocotyl cells of rapeseed (Brassica napus) and suspension cultures of carrot (Daucus carota). Ultrastructural and fluorescence analysis of cell aggregates from these protoplasts, cultured under microgravity conditions, have been performed. In the flight samples as well as in the ground controls, a portion of the total number of protoplasts regenerated cell walls. The processes of cell differentiation and proliferation under micro-g did not differ significantly from those under normal gravity conditions. However, in micro-g differences were observed in the ultrastructure of some organelles such as plastids and mitochondria. There was also an increase in the frequency of the occurrence of folds formed by the plasmalemma together with an increase in the degree of complexity of these folds. In cell cultures developed under micro-g conditions, the calcium content tends to decrease, compared to the ground control. Different aspects of using isolated protoplasts for clarifying the mechanisms of biological effects of microgravity are discussed.     

Comparative study of spermatogonial survival after x-ray exposure, high LET (HZE) irradiation or spaceflight.

Spermatogonial cell loss has been observed in rats flown on Space Lab 3, Cosmos 1887, Cosmos 2044 and in mice following irradiation with X-ray or with high energy (HZE) particle beams. Spermatogonial loss is determined by cell counting in maturation stage 6 seminiferous [correction of seminferous] tubules. With the exception of Iron, laboratory irradiation experiments (with mice) revealed a similar pattern of spermatogonial loss proportional to the radiation dose at levels less than 0.1 Gy. Helium and Argon irradiation resulted in a 5% loss of spermatogonia after only 0.01 Gy exposure. However, significant spermatogonial loss (45%) occured at this radiation level with Iron particle beams. The loss of spermatogonia during each space flight was less than 10% when compared to control (non-flight) animals. This loss, although small, was significant. Although radiation may be a contributing factor in the loss of spermatogonia during space flight, exposure levels, as determined by dosimetry, were not significant to account for the total cell loss observed.     

An Outline of Investigation of Space Medicine Problem and Its Mechanism

The human exploration of space is one of the great voyages of discovery in human history. For over forty years space exploration, human have gotten more profound knowledge about outer space and life phenomena, ranging from understanding and recognizing space to adapting and utilizing space. With these development, space medicine that aimed at studying effect of space environment on human health and ensuring the safety, health and effective working of human in space exploration, will become increasingly improved and matured.The contents of research will develop from the early phenomena observation of the effect of space environment on human physiology and biochemistry, and the effect definition, to the study of the mechanism of changes of cell, molecule, and gene, from the passive adaptation for space environment to taking the initiative countermeasures, in order to ensure the safety, health and effective working of astronauts during space flight.Space practices in the past forty years have confirmed that a variety of physiological and pathological changes have been found for organism exposed to space flight. These changes include cardiovascular dysfunction, bone loss,muscle atrophy, decline of immune function, endocrine function disorder and space motion sickness. In recent years, more attention has been focused on the study of the mechanism of these changes, especially the effects of space environment on cell, molecule and its gene expression. With the demand of China's manned space engineering task and continuous development, a series of studies on medical problem caused by space environment have been carried out.     

Seedling growth and development on space shuttle.

Young pine seedlings, and mung bean and oat seeds were flown on shuttle flights, STS-3 and STS-51F, in March, 1982 and July/August, 1985, respectively. The plant growth units built to support the two experiments functioned mechanically as anticipated and provided the necessary support data. Pine seedlings exposed to the microgravity environment of the space shuttle for 8 days continued to grow at a rate similar to ground controls. Pine stems in flight seedlings, however, averaged 10 to 12% less lignin than controls. Flight mung beans grew slower than control beans and their stems contained about 25% less lignin than control seedlings. Reduced mung bean growth in microgravity was partly due to slower germination rate. Lignin also was reduced in flight oats as compared to controls. Oats and mung beans exhibited upward growing roots which were not observed in control seedlings. Chlorophyll A/B ratios were lower in flight tissues than controls. The sealed PGCs exhibited large variations in atmospheric gas composition but the changes were similar between flight and ground controls. Ethylene was present in low concentrations in all chambers.     

Effects of space flight on surface marker expression.

Space flight has been shown to affect expression of several cell surface markers. These markers play important roles in regulation of immune responses, including CD4 and CD8. The studies have involved flight of experimental animals and humans followed by analysis of tissue samples (blood in humans, rats and monkeys, spleen, thymus, lymph nodes and bone marrow in rodents). The degree and direction of the changes induced by space flight have been determined by the conditions of the flight. Also, there may be compartmentalization of the response of surface markers to space flight, with differences in the response of cells isolated from blood and local immune tissue. The same type of compartmentalization was also observed with cell adhesion molecules (integrins). In this case, the expression of integrins from lymph node cells differed from that of splenocytes isolated from rats immediately after space flight. Cell culture studies have indicated that there may be an inhibition in conversion of a precursor cell line to cells exhibiting mature macrophage characteristics after space flight, however, these experiments were limited as a result of technical difficulties. In general, it is clear that space flight results in alterations of cell surface markers. The biological significance of these changes remains to be established.